[REDACTED] plans to carry out a Phase 1/2 study to evaluate the safety and efficacy of [REDACTED] for the treatment of β-Thalassemia Major(BTM). [REDACTED] consists of autologous patient hematopoietic stem cells(HSC) that have been genetically modified ex vivo with a lentiviral vector that encodes a therapeutic form of the β-globin gene. [REDACTED] is administered through autologous hematopoietic cell transplant(HCT), with the goal of restoring normal levels of hemoglobin and red blood cell(RBC) production in BTM patients who are dependent on RBC transfusions for survival.

Because they cannot produce functional hemoglobin, BTM patients require lifelong RBC transfusions that cause widespread organ damage from iron overload. While hemosiderosis can be mitigated with chelation therapy, poor compliance, efficacy and tolerability remain key challenges, and a majority BTM patients die in their 3rd-5th decade. The only cure for BTM is allogeneic HCT, which carries a significant risk of mortality and morbidity from immune-incompatibility between the donor and recipient, and is hampered by the limited availability of HLA matched sibling donors.

By stably inserting functional copies of β-globin into the genome of a patient’s own HSC, treatment with [REDACTED] promises to be a one-time transformative therapy for BTM. The β-globin gene in the [REDACTED] vector carries a single codon mutation [REDACTED] that allows for quantitative monitoring of therapeutic globin production but that does not alter oxygen carrying capacity. Treatment with an earlier version of the vector has been shown to correct β-thalassemia in mice [REDACTED]. In a clinical trial [REDACTED], 3 BTM patients were treated–one of whom became transfusion independent 1 year after treatment and remains so 4 years later.

Given the prevalence of patients with a common BTM genotype in California, [REDACTED] plans to open at least 2, and up to 4, clinical sites in California. Development activities are on track to initiate the trial in 1H 2013, and to complete the trial with 2 years of follow-up within the award window. [REDACTED] has completed a pre-IND meeting with the FDA and successfully manufactured a GMP lot of [REDACTED] vector that is available for clinical use. The Company expects to complete all IND enabling activities by Q4 2012.

In the last year, the company has made scientific advances that have allowed for a significant improvement in the efficiency of HSC genetic modification that will be help ensure clinical efficacy in BTM. Moreover, through collaborations with contract manufacturers, [REDACTED] is now producing large scale GMP lots of vector, and is on track to qualify a GMP cell processing facility with commercial capabilities prior to study initiation. [REDACTED].

Statement of Benefit to California:

The company expects to spend a major component of its financial resources conducting business within the state of California during the period of this CIRM award. Specifically: 1) we will have at least two clinical sites in California, and more likely up to 4 sites, 2) our viral vector manufacturing will occur in California, 3) our cell processing will occur in California, 4) we will hire several consultants and full-time employees within California to support the program. Overall, several million dollars will be spent employing the services of people, academic institutions, and other companies within the state of California.

Moreover, the disease we aim to treat occurs at a substantially greater rate of in California than other parts of the United States. As such, it is a significant public health concern, for which our therapy could provide a dramatically improved outcome and significant reduction in the lifetime cost of treatment, along with increased productivity. Due to the prevalence of the disease in California, if brought to the market, the pharmacoeconomic and social benefit of our therapy will accrue disproportionately to the state of California.